A Porphyrin Dimer–GdDOTA Conjugate as a Theranostic Agent for One- and Two-Photon Photodynamic Therapy and MRI

Julie Schmitt (1) , Sébastien Jenni (1) , Angélique Sour (1) , Valérie Heitz (1) , Frédéric Bolze (2) , Agnès Pallier (3) , Célia Bonnet (3) , Éva Tóth (3) , Barbara Ventura (4)

1 Institut de Chimie de Strasbourg
2 CAMB - Conception et application de molécules bioactives
3 CBM - Centre de biophysique moléculaire
4 ISOF-CNR - Istituto per la Sintesi Organica e la Fotoreattività

A molecular theranostic agent designed for photodynamic therapy (PDT) treatment in the near-infrared and for imaging tissue tumors with magnetic resonance imaging (MRI) is reported. It consists of a linear pi-conjugated Zn(II) porphyrin dimer linked at each extremity to a GdDOTA-type complex. This agent has shown very promising potential for PDT applications with good singlet oxygen generation in DMSO and high linear absorption in the near- infrared (lambda(max) = 746 nm, epsilon approximate to 10(5) M-1 cm(-1)). Moreover, this molecule has a propensity for two-photon excited PDT with high two-photon cross sections (similar to 8000 GM in 880-930 nm range), which should allow for deeper tumor treatments and higher spatial precision as compared to conventional one-photon PDT. Regarding the MRI contrast agent properties, the molecule has shown superior relaxivity (14.4 mM(-1) s(-1) at 40 MHz, 298 K) in comparison to clinical contrast agents and the ability to be internalized in cells, thanks to its amphiphilic character. Irradiation of HeLa cells using either one-photon (740 nm) or two-photon excitation (910 nm) has led in both cases to important cell death.

Domaines: Sciences du Vivant [q-bio]

Julie Schmitt, Sébastien Jenni, Angélique Sour, Valérie Heitz, Frédéric Bolze, et al.. A Porphyrin Dimer–GdDOTA Conjugate as a Theranostic Agent for One- and Two-Photon Photodynamic Therapy and MRI. Bioconjugate Chemistry, 2018, 29 (11), pp.3726-3738. ⟨10.1021/acs.bioconjchem.8b00634⟩. ⟨hal-02071234⟩